Accumulating evidence strongly associates human papillomavirus (HPV) infection with the development of anogenital cancers. The rising rate of specific anogenital cancers in HIV infected individuals has led researchers to begin the study HPV as a co-morbid infection in this group. Unfortunately, little data is available to date on HPV infections in HIV infected adults and even less information is available in adolescents. With the increased life expectancy of HIV infected persons, the rates of anogenital cancers can be expected to continue to rise. The purpose of this study is 1) to define the prevalence of HPV infection and HPV-related disease [(low and high grade squamous intraepithelial lesions) LGSIL/HGSIL] of the anogenital area (i.e. cervix, vagina, vulva,anus, penis, and scrotum) in adolescents infected with HIV and to compare the prevalence and severity of HPV disease in a group of similar high risk adolescents who are HIV negative (controls); 2) to define the natural history of HPV in HIV infected youth and to compare the rate of progression of HPV-related disease in HIV infected youth to the controls and 3) to examine the association between specific risk factors (specifically, high level HPV persistence, level of immunosuppression, substance use, hormonal influences, tobacco, and co-infections in the genital tract including Chlamydia trachomatis (CT), herpes simplex virus (HSV), cytomegalovirus (CMV), Treponema pallidum, Haemophilus ducreyi, fungal infections and Neisseria gonorrhoeae (NG) and HPV infection and the development of HPV-related disease in the anogenital tract in HIV infected youth. Methods: The 100 HIV positive and 100 HIV negative adolescents matched for similar high risk behavior (e.g. substance use, sexual behavior) collected by the Adolescent AIDS/HIV Research Network will be asked to participate. All adolescents will be asked to undergo a face-to- face interview, testing for HPV DNA, cervical, vaginal and anal cytology, CT, NG, HSV, CMV, T. pallidum, H. ducreyi, fungal infections, and bacterial vaginosis and colposcopic examination of the cervix, vagina, vulva, anus, penis and scrotum (gender appropriate). In addition, lavages of the cervical and anal mucous will be obtained for nicotine/cotinine assays. Patients will be asked to return every 4 months for similar examination and testing. All LGSIL will be followed. However, adolescents found to have evidence of HGSIL anywhere in the anogenital tract will be referred for treatment but continued to be followed after treatment is completed. Data analysis will emphasize the examination of differences for prevalence and disease severity of HPV-associated lesions between HIV positive and negative persons. The results from this study will be related to the prevention and education of pre-cancer and cancer lesions in adolescents infected with HIV.